Results CBF and MCA
3- Chez le sujet sain
Les études complémentaires portant sur l’analyse de l’influence sympathique sur le débit sanguin cérébral consistent en l’administration d’agents sympathomimétiques au repos chez le volontaire sain. Ainsi, en faisant varier cette fois non pas le débit cardiaque, mais la PAM isolément, Brassard retrouvait en 2009 une diminution de la vitesse moyenne enregistrée sur l’ACM après perfusion de noradrénaline chez 9 patients, laquelle entrainait une élévation de la PAM dose dépendante, à débit cardiaque constant [82] (Fig. 26). De même les paramètres d’oxygénation cérébrale mesurés se voyaient diminués : rSO2 (mesurée par
NIRS) et SvjO2 (oxygénation du lobe frontal mesurée en spectroscopie de proche infrarouge
et saturation veineuse jugulaire interne en oxygène). La diminution de l’oxygénation cérébrale pouvait être interprétée comme étant liée à l’élévation probable de la CMRO2 induite par
l’élévation de la PPC, à apports constants, le débit cardiaque n’étant pas augmenté.
3- Chez le sujet sain
Les études complémentaires portant sur l’analyse de l’influence sympathique sur le débit sanguin cérébral consistent en l’administration d’agents sympathomimétiques au repos chez le volontaire sain. Ainsi, en faisant varier cette fois non pas le débit cardiaque, mais la PAM isolément, Brassard retrouvait en 2009 une diminution de la vitesse moyenne enregistrée sur l’ACM après perfusion de noradrénaline chez 9 patients, laquelle entrainait une élévation de la PAM dose dépendante, à débit cardiaque constant [82] (Fig. 26). De même les paramètres d’oxygénation cérébrale mesurés se voyaient diminués : rSO2 (mesurée par
NIRS) et SvjO2 (oxygénation du lobe frontal mesurée en spectroscopie de proche infrarouge
et saturation veineuse jugulaire interne en oxygène). La diminution de l’oxygénation cérébrale pouvait être interprétée comme étant liée à l’élévation probable de la CMRO2 induite par
Fig. 26 Evolution de la pression artérielle moyenne (MAP), de la vitesse moyenne de l’artère sylvienne
(MCAVmean), de l’oxygénation du lobe frontal (ScO2 ou rSO2) et de la saturation veineuse jugulaire en oxygène
(SjvO2) après administration de doses croissantes de la noradrénaline. *p < 0,05 †p < 0,01 versus sérum
physiologique. D’après Brassard et al [82].
A l’inverse, Seifert ne retrouvait pas d’altération de la vélocité moyenne sur l’ACM après perfusion d’adrénaline (cette fois possédant une action β adrénergique) chez des volontaires sains au repos [83]. L’administration d’éphédrine (à la fois α et β mimétique) après induction de l’anesthésie générale responsable d’une hypotension artérielle, maintenait une oxygénation cérébrale satisfaisante, potentiellement en lien avec une augmentation du débit cardiaque, contrairement à la phényléphrine [84].
Discussion
The present results suggest that although the infusion of nor- epinephrine increases MAP by peripheral vasoconstriction in a dose–response manner, leading to an elevation in eCPP, it also negatively affects cerebral oxygenation, characterized
by a reduction in both ScO2and SjvO2, reaching a statistical
significant reduction in this study with the infusion of 0.1 mg kg21min21or higher dose.
The maintenance of an adequate perfusion is important for vital organs such as the brain. On the basis of the studies reporting no impact or only a small reduction in CBF with administration of norepinephrine,10 11 the
elevation of CPP in situations during which the brain per- fusion is challenged has been thought to be safely under- taken by increasing MAP. However, the influence of norepinephrine on cerebral haemodynamics is ambiguous. Strebel and colleagues20 reported an increase in MCA
Vmean after the administration of norepinephrine titrated to increase MAP 20% above baseline value, but suggested that in these anaesthetized patients, the augmentation in MCA Vmean was influenced by the effect of the anaes- thetic agents on cerebral autoregulation. In order to rule out the impact of anaesthesia on cerebral autoregulation, Moppett and colleagues9 gradually infused 0.02 – 0.1 mg
kg21min21of norepinephrine to awake healthy subjects
and increased MAP by 25% with no change in MCA Vmean. This observation was explained by an increase in cerebrovascular tone expressed as ZFP, resulting in no change in eCPP. In the present study, the infusion of 0.1 mg kg21
min21 of norepinephrine increased MAP by !23% leading to an elevation in eCPP without signifi- cantly increasing cerebrovascular tone expressed as ZFP, but in constrast to the findings by Moppett and colleagues, it lowered MCA Vmean. Increasing the dose of norepi- nephrine to 0.15 mg kg21min21produced similar results except that ZFP also increased. This reduction in MCA Vmean could be considered small, but since cerebral vas- culature possess sympathetic innervation,21it may be that
the infusion of norepinephrine had a direct vasoconstrictor effect on the MCA, transiently increasing MCA Vmean and thus, underestimating the reduction in CBF. However, whether changes in MCA Vmean represent changes in CBF with infusion of norepinephrine remains to be proven.
The novel finding of the present study is the reduction in cerebral oxygenation after the infusion of norepi- nephrine to healthy subjects. The infusion of 0.1 and 0.15 mg kg21 min21 of norepinephrine led to a reduction
of!8% and !3% in ScO2and SjvO2respectively, and a
10 – 15% reduction in ScO2is associated with presyncopal
symptoms.22 Although the spectrometer is spatially
resolved, the lower reduction in SjvO2compared with ScO2
could be related to a diminution in skin blood flow from the frontal area measured by the NIRS apparatus after the infusion of norepinephrine. As ScO2 mainly reflects the
venous compartment, we could expect that a reduction in ScO2 represents to some extent a reduction in SjvO2,
especially with an arterial oxygen saturation most likely stable in healthy subjects. Furthermore, the concomitant reductions in three flow-related signals, for example, MCA Vmean, ScO2and SjvO2, suggest that cerebral oxygenation
130 120 110 100 * * * * * † † * * 90 80 65 60 55 50 45 85 80 75 70 65 75 70 65 60 55 Saline S jvO 2 (%) S cO2 (%) MCA Vmean (cm s –1) MAP (mm Hg) 0.05
Doses of norepinephrine ( g kg–1 min–1)
0.1 0.15
Fig 1 MAP, MCA Vmean, frontal lobe oxygenation, and jugular venous oxygen saturation with increasing doses of norepinephrine. MAP, mean arterial pressure; MCA Vmean, middle cerebral artery mean flow velocity; ScO2, frontal lobe oxygenation; SjvO2, jugular venous oxygen
saturation; *P , 0.05 and†
P , 0.01 vs saline.
Norepinephrine and cerebral oxygenation
803
at CHU Grenoble on June 4, 2010
http://bja.oxfordjournals.org
Downloaded from
Fig. 26 Evolution de la pression artérielle moyenne (MAP), de la vitesse moyenne de l’artère sylvienne
(MCAVmean), de l’oxygénation du lobe frontal (ScO2 ou rSO2) et de la saturation veineuse jugulaire en oxygène
(SjvO2) après administration de doses croissantes de la noradrénaline. *p < 0,05 †p < 0,01 versus sérum
physiologique. D’après Brassard et al [82].
A l’inverse, Seifert ne retrouvait pas d’altération de la vélocité moyenne sur l’ACM après perfusion d’adrénaline (cette fois possédant une action β adrénergique) chez des volontaires sains au repos [83]. L’administration d’éphédrine (à la fois α et β mimétique) après induction de l’anesthésie générale responsable d’une hypotension artérielle, maintenait une oxygénation cérébrale satisfaisante, potentiellement en lien avec une augmentation du débit cardiaque, contrairement à la phényléphrine [84].
Discussion
The present results suggest that although the infusion of nor- epinephrine increases MAP by peripheral vasoconstriction in a dose–response manner, leading to an elevation in eCPP, it also negatively affects cerebral oxygenation, characterized
by a reduction in both ScO2and SjvO2, reaching a statistical
significant reduction in this study with the infusion of 0.1 mg kg21min21or higher dose.
The maintenance of an adequate perfusion is important for vital organs such as the brain. On the basis of the studies reporting no impact or only a small reduction in CBF with administration of norepinephrine,10 11 the
elevation of CPP in situations during which the brain per- fusion is challenged has been thought to be safely under- taken by increasing MAP. However, the influence of norepinephrine on cerebral haemodynamics is ambiguous. Strebel and colleagues20 reported an increase in MCA
Vmean after the administration of norepinephrine titrated to increase MAP 20% above baseline value, but suggested that in these anaesthetized patients, the augmentation in MCA Vmean was influenced by the effect of the anaes- thetic agents on cerebral autoregulation. In order to rule out the impact of anaesthesia on cerebral autoregulation, Moppett and colleagues9 gradually infused 0.02 – 0.1 mg
kg21min21of norepinephrine to awake healthy subjects
and increased MAP by 25% with no change in MCA Vmean. This observation was explained by an increase in cerebrovascular tone expressed as ZFP, resulting in no change in eCPP. In the present study, the infusion of 0.1 mg kg21
min21 of norepinephrine increased MAP by !23% leading to an elevation in eCPP without signifi- cantly increasing cerebrovascular tone expressed as ZFP, but in constrast to the findings by Moppett and colleagues, it lowered MCA Vmean. Increasing the dose of norepi- nephrine to 0.15 mg kg21min21produced similar results except that ZFP also increased. This reduction in MCA Vmean could be considered small, but since cerebral vas- culature possess sympathetic innervation,21it may be that
the infusion of norepinephrine had a direct vasoconstrictor effect on the MCA, transiently increasing MCA Vmean and thus, underestimating the reduction in CBF. However, whether changes in MCA Vmean represent changes in CBF with infusion of norepinephrine remains to be proven.
The novel finding of the present study is the reduction in cerebral oxygenation after the infusion of norepi- nephrine to healthy subjects. The infusion of 0.1 and 0.15 mg kg21 min21 of norepinephrine led to a reduction
of!8% and !3% in ScO2and SjvO2respectively, and a
10 – 15% reduction in ScO2is associated with presyncopal
symptoms.22 Although the spectrometer is spatially
resolved, the lower reduction in SjvO2compared with ScO2
could be related to a diminution in skin blood flow from the frontal area measured by the NIRS apparatus after the infusion of norepinephrine. As ScO2 mainly reflects the
venous compartment, we could expect that a reduction in ScO2 represents to some extent a reduction in SjvO2,
especially with an arterial oxygen saturation most likely stable in healthy subjects. Furthermore, the concomitant reductions in three flow-related signals, for example, MCA Vmean, ScO2and SjvO2, suggest that cerebral oxygenation
130 120 110 100 * * * * * † † * * 90 80 65 60 55 50 45 85 80 75 70 65 75 70 65 60 55 Saline S jvO 2 (%) S cO2 (%) MCA Vmean (cm s –1) MAP (mm Hg) 0.05
Doses of norepinephrine ( g kg–1 min–1)
0.1 0.15
Fig 1 MAP, MCA Vmean, frontal lobe oxygenation, and jugular venous oxygen saturation with increasing doses of norepinephrine. MAP, mean arterial pressure; MCA Vmean, middle cerebral artery mean flow velocity; ScO2, frontal lobe oxygenation; SjvO2, jugular venous oxygen
saturation; *P , 0.05 and†
P , 0.01 vs saline.
Norepinephrine and cerebral oxygenation
803
at CHU Grenoble on June 4, 2010
http://bja.oxfordjournals.org
Pour résumer, les volontaires sains soumis à la perfusion d’amines sympathomimétiques voyaient leur débit sanguin cérébral maintenu et leur oxygénation cérébrale conservée, sous condition d’une stimulation β adrénergique responsable d’une élévation du débit cardiaque associée à l’élévation de la PAM. A l’inverse, une stimulation α mimétique isolée faisant croître la PAM était responsable d’une chute du DSC à débit cardiaque constant.